440 results on '"Poon RT"'
Search Results
2. IMPROVEMENT IN LONG-TERM SURVIVAL AFTER MAJOR HEPATIC RESECTION FOR SMALL SOLITARY HEPATOCELLULAR CARCINOMA IN CIRRHOTIC PATIENTS: 837
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Wong, TCL, Cheung, TT, Chok, KS, Chan, AC, Tsang, SH, and Poon, RT
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- 2013
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3. Serine peptidase inhibitor Kazal type 1 (SPINK1) as novel downstream effector of the cadherin-17/beta-catenin axis in hepatocellular carcinoma
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Skec, FHS, Lou, R, Lam, YHB, Sung, WKS, Lam, T-W, Luk, JM, Leung, MS, Chan, KT, Poon, RT, Lee, NP, Lam, Brian [0000-0002-3638-9025], and Apollo - University of Cambridge Repository
- Subjects
SPINK1 ,CDH17/β-catenin axis ,CDH17 ,HCC ,neoplasms ,digestive system diseases - Abstract
Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Previously, we reported that cadherin-17 (CDH17) and its related CDH17/-catenin axis may be responsible for inducing HCC in a subset of patients exhibiting CDH17 over-expression. Here we aimed at obtaining a better understanding of the CDH17-related HCC biology and to obtain further indications for the design of targeted therapies in CDH17 over-expressing HCC patients. Results: We found that SPINK1 acts as a downstream effector of the CDH17/-catenin axis in HCC. In addition, we found that SPINK1 expression exhibited a positive correlation with CDH17 expression in human HCCs and was over-expressed in up to 70% of the tumors. We identified SPINK1 as a downstream effector of the CDH17/-catenin axis using a spectrum of in vitro assays, including gene expression modulation and inhibitor assays, bioinformatics analyses and luciferase reporter assays. These in vitro results were validated in primary human HCCs, including the observation that alteration in -catenin expression (a core component of the CDH17/-catenin axis) in tumors affects SPINK1 serum levels in HCC patients. Similar to CDH17, SPINK1 expression in HCC cells was found to be associated with specific tumor-related properties via activating the c-Raf/MEK/ERK pathway. Conclusions: Our current data substantiate our knowledge on the role of CDH17 in the biology of HCC and suggest that components of the CDH17/-catenin axis may serve as therapeutic targets in CDH17 over-expressing HCC patients.
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- 2017
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4. Improving perioperative outcome expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases: analysis of 1222 consecutive patients from a prospective database
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Yeung, C, Pitt, HA, Yuen, WK, Liu, CL, Henderson, JM, Lam, CM, Nagorney, DM, Poon, RT, Fan, ST, Lo, CM, and Wong, J
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Adult ,Male ,medicine.medical_specialty ,Biomedical Research ,Blood transfusion ,Carcinoma, Hepatocellular ,Family Practice - trends ,medicine.medical_treatment ,Blood Loss, Surgical ,Bile Duct Diseases ,Lithiasis ,Gastroenterology ,Original Articles and Discussions ,Bile Ducts, Extrahepatic ,Internal medicine ,medicine ,Hepatectomy ,Humans ,Blood Transfusion ,Hypoalbuminemia ,Prospective Studies ,Prospective cohort study ,Aged ,business.industry ,Patient Selection ,Hepatobiliary disease ,Liver Neoplasms ,Age Factors ,Perioperative ,Middle Aged ,medicine.disease ,Thrombocytopenia ,Surgery ,Bile Ducts, Intrahepatic ,Treatment Outcome ,Bile Duct Neoplasms ,Databases as Topic ,Creatinine ,Hong Kong ,Female ,Liver function ,Hepatolithiasis ,business ,Forecasting - Abstract
Objective: To assess the trends in perioperative outcome of hepatectomy for hepatobiliary diseases. Methods: Data of 1222 consecutive patients who underwent hepatectomy for hepatobiliary diseases from July 1989 to June 2003 in a tertiary institution were collected prospectively. Perioperative outcome of patients in the first (group I) and second (group II) halves of this period was compared. Factors associated with morbidity and mortality were analyzed. Results: Diagnoses included hepatocellular carcinoma (n = 734), other liver cancers (n = 257), extrahepatic biliary malignancies (n = 43), hepatolithiasis (n = 101), benign liver tumors (n = 61), and other diseases (n = 26). The majority of patients (61.8%) underwent major hepatectomy of ≥3 segments. The overall hospital mortality and morbidity were 4.9% and 32.4%, respectively. The number of hepatectomies increased from 402 in group I to 820 in group II, partly as a result of more liberal patient selection. Group II had more elderly patients (P = 0.006), more patients with comorbid illnesses (P = 0.001), and significantly worse liver function. Nonetheless, group II had lower blood loss (median 750 versus 1450 mL, P < 0.001), perioperative transfusion (17.3% versus 67.7%, P < 0.001), morbidity (30.0% versus 37.3%, P = 0.012), and hospital mortality (3.7% versus 7.5%, P = 0.004). On multivariate analysis, hypoalbuminemia, thrombocytopenia, elevated serum creatinine, major hepatic resection, and transfusion were the significant predictors of hospital mortality, whereas concomitant extrahepatic procedure, thrombocytopenia, and transfusion were the predictors of morbidity. Conclusions: Perioperative outcome has improved despite extending the indication of hepatectomy to more high-risk patients. The role of hepatectomy in the management of hepatobiliary diseases can be expanded. Reduced perioperative transfusion is the main contributory factor for improved outcome., published_or_final_version
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- 2004
5. Abstract 3862: The potential role of CD44 in liver regeneration
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Lam, CT, primary, Yang, ZF, additional, Ng, MN, additional, Wan, T, additional, Lau, J, additional, Ho, DW, additional, Fan, ST, additional, and Poon, RT, additional
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- 2012
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6. SPARC and Hevin expression correlate with tumour angiogenesis in hepatocellular carcinoma
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Lau, CP-Y, primary, Poon, RT-P, additional, Cheung, S-T, additional, Yu, W-C, additional, and Fan, S-T, additional
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- 2006
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7. PIN1 expression contributes to hepatic carcinogenesis
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Pang, RW, primary, Lee, TK, additional, Man, K, additional, Poon, RT, additional, Fan, S‐T, additional, Kwong, Y‐L, additional, and Tse, E, additional
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- 2006
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8. Phase 1-2 trial of PTK787/ZK222584 combined with intravenous doxorubicin for treatment of patients with advanced hepatocellular carcinoma: implication for antiangiogenic approach to hepatocellular carcinoma.
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Yau T, Chan P, Pang R, Ng K, Fan ST, and Poon RT
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- 2010
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9. Phase 2 open-label study of single-agent sorafenib in treating advanced hepatocellular carcinoma in a hepatitis B-endemic Asian population: presence of lung metastasis predicts poor response.
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Yau T, Chan P, Ng KK, Chok SH, Cheung TT, Fan ST, and Poon RT
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- 2009
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10. Changes in liver histology as a 'surrogate' end point of antiviral therapy for chronic HBV can predict progression to liver complications.
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Hui CK, Leung N, Shek WH, Zhang HY, Luk JM, Poon RT, Lo CM, Fan ST, Lau GK, and Hong Kong Liver Fibrosis Study Group
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- 2008
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11. Yttrium-90 radioembolization for advanced inoperable hepatocellular carcinoma
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Lee VHF, Leung DKC, Luk MY, Tong CC, Law MWM, Ng SCY, Wong KK, Poon RTP, Kwong DLW, and Leung TW
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Victor Ho-Fun Lee,1,* Dennis KC Leung,1,* Mai-Yee Luk,1 Chi-Chung Tong,1 Martin WM Law,2 Sherry CY Ng,1 Ka-Kin Wong,3 Ronnie TP Poon,4 Dora LW Kwong,1 To-Wai Leung1 1Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 2Department of Nuclear Medicine, 3Department of Radiology, Queen Mary Hospital, 4Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong *These authors contributed equally to this work Background: Advanced inoperable hepatocellular carcinoma (HCC) conferring a grave prognosis may benefit from yttrium-90 (90Y) radioembolization.Methods: Thirty patients with advanced inoperable HCC including those with any lesion >8 cm in maximal diameter or multiple bi-lobar lesions (totally more than five lesions), or portal vein thrombosis treated with radioembolization were reviewed. Treatment efficacy and safety were evaluated. Univariate and multivariate analyses were performed for identifying potential prognostic factors.Results: After a median follow-up of 18.3 months, the response rate was 30.0%, and the disease control rate was 50.0%. Median overall progression-free survival (PFS) and overall survival (OS) were 3.3 months and 13.2 months, respectively. Longer median PFS was noted in those who had transarterial chemoembolization before radioembolization (7.3 months vs 3.1 months; P=0.021) and duration of alfa-feto protein (AFP) response ≥6 months (11.8 months vs 3.0 months; P
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- 2015
12. Overexpression of Pin1 and rho signaling partners correlates with metastatic behavior and poor recurrence-free survival of hepatocellular carcinoma patients.
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Ng L, Kwan V, Chow A, Yau TC, Poon RT, Pang R, and Law WL
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- Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular surgery, Disease Progression, Disease-Free Survival, Female, Humans, Liver Neoplasms surgery, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local, Neoplasm Staging, Postoperative Care, Prognosis, RNA, Messenger genetics, Random Allocation, Young Adult, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular secondary, Liver Neoplasms mortality, Liver Neoplasms pathology, NIMA-Interacting Peptidylprolyl Isomerase metabolism, rhoA GTP-Binding Protein metabolism, rhoC GTP-Binding Protein metabolism
- Abstract
Background: Identification of molecular markers for early detection or prediction of metastasis is crucial for both management of HCC patient postoperative treatment and identify new therapeutic targets to inhibit HCC progression and metastasis. In the current study, we investigated the clinical correlation between Pin1, RhoA and RhoC and their association with HCC metastasis., Methods: Using a randomized study design of primary HCC samples from 139 patients, we determined messenger RNA expression of Pin1, RhoA and RhoC and their prognostic value., Results: Our findings demonstrated for the first time the clinical correlation of Pin1 in HCC metastasis. Pin1, RhoA and RhoC transcript levels were significantly higher in HCC specimens when compared with the paired adjacent non-tumorous liver. Pin1 overexpression was closely correlated with that of RhoA (R = 0.562, p < 0.001) and RhoC (R = 0.529, p < 0.001), and their co-overexpressions correlated with metastatic HCC (p = 0.000012) and poor recurrence-free survival of HCC patients (p < 0.00001), which showed better prognostic significance than either Pin1, RhoA or RhoC overexpression alone. Co-overexpressions of Pin1 + RhoA/RhoC were also an independent factor for predicting development of metastasis after curative resection in our multivariate regression model (p < 0.001)., Conclusion: Pin1, RhoA and RhoC co-overexpressions are prognostic factor for metastatic HCC and predict poor recurrence-free survival.
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- 2019
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13. An N-terminal truncated carboxypeptidase E splice isoform induces tumor growth and is a biomarker for predicting future metastasis in human cancers.
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Lee TK, Murthy SR, Cawley NX, Dhanvantari S, Hewitt SM, Lou H, Lau T, Ma S, Huynh T, Wesley RA, Ng IO, Pacak K, Poon RT, and Loh YP
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- 2019
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14. Prevention of post-sphincterotomy bleeding by proton pump inhibitor: A randomized controlled trial.
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Leung WK, But DY, Wong SY, Tong TS, Liu KS, Cheung KS, Tsang SH, Chok KS, Poon RT, and Hung IF
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- Aged, Aged, 80 and over, Cholangiopancreatography, Endoscopic Retrograde adverse effects, Drug Administration Schedule, Esomeprazole administration & dosage, Esomeprazole therapeutic use, Female, Humans, Male, Middle Aged, Postoperative Hemorrhage etiology, Postoperative Period, Preoperative Care methods, Proton Pump Inhibitors administration & dosage, Postoperative Hemorrhage prevention & control, Proton Pump Inhibitors therapeutic use, Sphincterotomy, Endoscopic adverse effects
- Abstract
Objective: Post-endoscopic sphincterotomy (EST) bleeding is one of the most frequent complications of endoscopic retrograde cholangiopancreatography (ERCP). Although the use of proton pump inhibitors (PPIs) reduces the risk of peptic ulcer bleeding, their role in preventing EST bleeding has not been evaluated. This study aimed to assess the use of pre-emptive PPIs in patients undergoing EST., Methods: This was an investigator-initiated, open-label, randomized study. Consecutive patients scheduled to undergo ERCP and EST were enrolled after excluding those who had previous EST or used acid-suppression agents. Eligible patients were randomized to receive either PPI or standard care. The PPI group received intravenous esomeprazole 4 h before the EST and then every 12 h for 1 day, followed by high-dose oral esomeprazole for 10 days. All patients were followed up for 30 days. The primary outcome was the proportion of patients with combined immediate and delayed overt post-EST bleeding., Results: Altogether 125 patients (60 in the PPI arm and 65 in the standard care arm) who had undergone EST were analyzed. Immediate bleeding was noted in nine (15.0%) patients in the PPI group and four (6.2%) in the standard care group (P = 0.14). Overt delayed post-EST bleeding was seen in two (3.3%) and five (7.7%) patients in PPI and standard care arms, respectively (P = 0.44). There were no significant differences in other outcomes, including a decrease in hemoglobin of >20 g/L, the need for blood transfusion, length of hospital stay and 30-day mortality., Conclusion: Pre-emptive PPI did not reduce the risk of post-EST bleeding., (© 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)
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- 2018
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15. Serine peptidase inhibitor Kazal type 1 (SPINK1) as novel downstream effector of the cadherin-17/β-catenin axis in hepatocellular carcinoma.
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Shek FH, Luo R, Lam BYH, Sung WK, Lam TW, Luk JM, Leung MS, Chan KT, Wang HK, Chan CM, Poon RT, and Lee NP
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- Cadherins metabolism, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cell Line, Cell Line, Tumor, Cohort Studies, Gene Expression Profiling methods, Gene Expression Regulation, Neoplastic, Hep G2 Cells, Humans, Liver Neoplasms metabolism, Liver Neoplasms pathology, RNA Interference, Signal Transduction genetics, Trypsin Inhibitor, Kazal Pancreatic blood, Trypsin Inhibitor, Kazal Pancreatic metabolism, beta Catenin metabolism, Cadherins genetics, Carcinoma, Hepatocellular genetics, Liver Neoplasms genetics, Trypsin Inhibitor, Kazal Pancreatic genetics, beta Catenin genetics
- Abstract
Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Previously, we reported that cadherin-17 (CDH17) and its related CDH17/β-catenin axis may be responsible for inducing HCC in a subset of patients exhibiting CDH17 over-expression. Here we aimed at obtaining a better understanding of the CDH17-related HCC biology and to obtain further indications for the design of targeted therapies in CDH17 over-expressing HCC patients., Results: We found that SPINK1 acts as a downstream effector of the CDH17/β-catenin axis in HCC. In addition, we found that SPINK1 expression exhibited a positive correlation with CDH17 expression in human HCCs and was over-expressed in up to 70% of the tumors. We identified SPINK1 as a downstream effector of the CDH17/β-catenin axis using a spectrum of in vitro assays, including gene expression modulation and inhibitor assays, bioinformatics analyses and luciferase reporter assays. These in vitro results were validated in primary human HCCs, including the observation that alteration in β-catenin expression (a core component of the CDH17/β-catenin axis) in tumors affects SPINK1 serum levels in HCC patients. Similar to CDH17, SPINK1 expression in HCC cells was found to be associated with specific tumor-related properties via activating the c-Raf/MEK/ERK pathway., Conclusions: Our current data substantiate our knowledge on the role of CDH17 in the biology of HCC and suggest that components of the CDH17/β-catenin axis may serve as therapeutic targets in CDH17 over-expressing HCC patients.
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- 2017
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16. Differences in health-related quality of life between European and Asian patients with hepatocellular carcinoma.
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Chie WC, Blazeby JM, Hsiao CF, Chiu HC, Poon RT, Mikoshiba N, Al-Kadhim G, Heaton N, Calara J, Collins P, Caddick K, Costantini A, and Vilgrain V
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- Aged, Asian People, Carcinoma, Hepatocellular pathology, Cross-Sectional Studies, Europe, Female, Humans, Liver Neoplasms pathology, Male, Middle Aged, Surveys and Questionnaires, Carcinoma, Hepatocellular psychology, Liver Neoplasms psychology, Quality of Life psychology
- Abstract
Aim: The aim of this study is to explore the possible effects of clinical and cultural characteristics of hepatocellular carcinoma on patients' health-related quality of life (HRQoL)., Methods: Patients with hepatocellular carcinoma from Asian and European countries completed the EORTC QLQ-C30 and the EORTC QLQ-HCC18. Comparisons were made using Student's t-test and Wilcoxon rank-sum test with method of false discovery to correct multiple comparisons. Multiway analysis of variance and model selection were used to assess the effects of clinical characteristics and geographic areas., Results: Two hundred and twenty-seven patients with hepatocellular carcinoma completed questionnaires. After adjusting for demographic and clinical characteristics, Asian patients still had significantly better HRQoL scores in emotional functioning, insomnia, (QLQ-C30) and in sexual interest (QLQ-HCC18). We also found an interaction in physical functioning (QLQ-C30) and fatigue (QLQ-HCC18) between geographic region and marital status, married European had worse HRQoL scores than Asian singles., Conclusions: Both clinical characteristics and geographic areas affected the HRQoL in with hepatocellular carcinoma. Cultural differences and clinical differences in the pattern of disease due to active surveillance of Asian countries may explain the results., (© 2016 John Wiley & Sons Australia, Ltd.)
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- 2017
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17. Emergence of CD26+ Cancer Stem Cells with Metastatic Properties in Colorectal Carcinogenesis.
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Cheung AH, Iyer DN, Lam CS, Ng L, Wong SKM, Lee HS, Wan T, Man J, Chow AKM, Poon RT, Pang R, and Law WL
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- Aged, Aged, 80 and over, Carcinogenesis pathology, Female, Humans, Male, Biomarkers, Tumor metabolism, Carcinogenesis metabolism, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Dipeptidyl Peptidase 4 metabolism, Neoplastic Stem Cells metabolism
- Abstract
Colorectal cancer results from genetic aberrations which accumulate over a long period of time, with malignant and metastatic properties acquired at a relatively late stage. A subpopulation of CD26+ colorectal cancer stem cells are known to be implicated in metastasis. We quantified CD26+ cancer cells in 11 primary tumor samples by flow cytometry, and showed that tumors having confirmed or suspected metastases harbored a relatively high CD26+ level in these samples. We hypothesized that this subpopulation of cancer stem cells arises in the late stage of carcinogenesis from the bulk of tumor daughter cells which are CD26-. The manipulation of PIK3CA and TP53 , two genes commonly deregulated in the late stage, had an effect on the maintenance of the CD26+ cell population. When CD26- tumor daughter cells were sorted and cultured, the emergence of tumor spheres containing CD26+ cells occurred. These findings shed light to the origin of colorectal cancer stem cells with metastatic properties, which has an implication on conventional treatments by surgery or adjuvant chemotherapy for tumor debulking., Competing Interests: The authors declare no conflict of interest.
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- 2017
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18. Nine-year experience of doxorubicin-eluting beads chemoembolization for hepatocellular carcinoma.
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Cheung AH, Lam CS, Tam HS, Cheung TT, Pang R, and Poon RT
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- Aged, Antibiotics, Antineoplastic adverse effects, Carcinoma, Hepatocellular blood, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Chi-Square Distribution, Doxorubicin adverse effects, Female, Hong Kong, Humans, Kaplan-Meier Estimate, Liver Neoplasms blood, Liver Neoplasms mortality, Liver Neoplasms pathology, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Retrospective Studies, Time Factors, Tomography, X-Ray Computed, Treatment Outcome, Tumor Burden, alpha-Fetoproteins metabolism, Antibiotics, Antineoplastic administration & dosage, Carcinoma, Hepatocellular therapy, Chemoembolization, Therapeutic adverse effects, Doxorubicin administration & dosage, Liver Neoplasms therapy
- Abstract
Background: Chemoembolization with doxorubucin-eluting beads (DEB) has been used to treat hepatocellular carcinoma (HCC) since 2007. This study compared the efficacy and survival between transarterial chemoembolization (TACE) with DEB and conventional approach (cTACE) in HCC treatment., Methods: This retrospective case-control study compared the overall survival and tumor response of HCC patients to cTACE (n=190) and DEB (n=143) by the reassessment of computed tomography and serum alpha-fetoprotein (AFP). Multivariate analysis was used to determine the factors affecting tumor response., Results: The median post-treatment to pre-treatment AFP level was 0.8 for a DEB session (n=258) and 1.0 for a cTACE session (n=452), showing a significantly greater decrease in AFP after DEB (P<0.05). More patients in the DEB group achieved objective response (complete and partial) compared with those in the cTACE group (P<0.05). Objective tumor response after DEB vs cTACE was 34.8% vs 15.4% in 0-3 months (P=0.001), 37.1% vs 20.0% in 3-6 months (P<0.05), and 50.0% vs 30.0% in 6-12 months (P=0.093). DEB predicted a 3.604 times odds of achieving at least one objective tumor response in a patient when compared to cTACE (P<0.0001). The median survival from first transcatheter therapy of patients having undergone at least once DEB was 12.53 months, while those having received cTACE only was 10.53 months (P=0.086). A tendency of improved survival appeared to maintain until >80 months after the first TACE session in the DEB group., Conclusion: DEB is a safe alternative to cTACE in HCC patients with better therapeutic efficacy.
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- 2016
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19. Surgery for Intermediate and Advanced Hepatocellular Carcinoma: A Consensus Report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014).
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Ho MC, Hasegawa K, Chen XP, Nagano H, Lee YJ, Chau GY, Zhou J, Wang CC, Choi YR, Poon RT, and Kokudo N
- Abstract
Background: The Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy does not recommended surgery for treating BCLC stage B and C hepatocellular carcinoma (HCC). However, numerous Asia-Pacific institutes still perform surgery for this patient group. This consensus report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting aimed to share opinions and experiences pertaining to liver resection for intermediate and advanced HCCs and to provide evidence to issue recommendations for surgery in this patient group., Summary: Thirteen experts from five Asia-Pacific regions were invited to the meeting; 10 of them (Japan: 2, Taiwan: 3, South Korea: 2, Hong Kong: 1, and China: 2) voted for the final consensus. The discussion focused on evaluating the preoperative liver functional reserve and surgery for large tumors, multiple tumors, HCCs with vascular invasion, and HCCs with distant metastasis. The feasibility of future prospective randomized trials comparing surgery with transarterial chemoembolization for intermediate HCC and with sorafenib for advanced HCC was also discussed. The Child-Pugh score (9/10 experts) and indocyanine green retention rate at 15 min (8/10) were the most widely accepted methods for evaluating the preoperative liver functional reserve. All (10/10) experts agreed that portal hypertension, tumor size >5 cm, portal venous invasion, hepatic venous invasion, and extrahepatic metastasis are not absolute contraindications for the surgical resection of HCC. Furthermore, 9 of the 10 experts agreed that tumor resection may be performed for patients with >3 tumors. The limitations of surgery are associated with a poor liver functional reserve, incomplete tumor resection, and a high probability of recurrence., Key Messages: Surgery provides significant survival benefits for Asian-Pacific patients with intermediate and advanced HCCs, particularly when the liver functional reserve is favorable. However, prospective randomized controlled trials are difficult to conduct because of technical and ethical considerations.
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- 2016
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20. Randomized, open-label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma.
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Cheng AL, Thongprasert S, Lim HY, Sukeepaisarnjaroen W, Yang TS, Wu CC, Chao Y, Chan SL, Kudo M, Ikeda M, Kang YK, Pan H, Numata K, Han G, Balsara B, Zhang Y, Rodriguez AM, Zhang Y, Wang Y, and Poon RT
- Subjects
- Adult, Aged, Aged, 80 and over, Animals, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacokinetics, Benzimidazoles adverse effects, Benzimidazoles pharmacokinetics, Biomarkers blood, Carcinoma, Hepatocellular blood, Carcinoma, Hepatocellular mortality, Cell Line, Tumor, Asia, Eastern epidemiology, Female, Humans, Liver Neoplasms blood, Liver Neoplasms mortality, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Middle Aged, Niacinamide adverse effects, Niacinamide pharmacokinetics, Niacinamide therapeutic use, Phenylurea Compounds adverse effects, Phenylurea Compounds pharmacokinetics, Quinolones adverse effects, Quinolones pharmacokinetics, Sorafenib, Treatment Outcome, Xenograft Model Antitumor Assays, Antineoplastic Agents therapeutic use, Benzimidazoles therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds therapeutic use, Quinolones therapeutic use
- Abstract
Unlabelled: Angiogenesis inhibition by the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic escape from sorafenib may occur due to angiogenesis-associated fibroblast growth factor receptor (FGFR) pathway activation. In addition to VEGFR and PDGFR, dovitinib inhibits FGFR. Frontline oral dovitinib (500 mg/day, 5 days on, 2 days off; n = 82) versus sorafenib (400 mg twice daily; n = 83) was evaluated in an open-label, randomized phase 2 study of Asian-Pacific patients with advanced HCC. The primary and key secondary endpoints were overall survival (OS) and time to tumor progression (TTP) as determined by a local investigator, respectively. Patients included in the study were ineligible for surgical and/or locoregional therapies or had disease progression after receiving these therapies. The median OS (95% confidence interval [CI]) was 8.0 (6.6-9.1) months for dovitinib and 8.4 (5.4-11.3) months for sorafenib. The median TTP (95% CI) per investigator assessment was 4.1 (2.8-4.2) months and 4.1 (2.8-4.3) months for dovitinib and sorafenib, respectively. Common any-cause adverse events included diarrhea (62%), decreased appetite (43%), nausea (41%), vomiting (41%), fatigue (35%), rash (34%), and pyrexia (30%) for dovitinib and palmar-plantar erythrodysesthesia syndrome (66%) and decreased appetite (31%) for sorafenib. Subgroup analysis revealed a significantly higher median OS for patients in the dovitinib arm who had baseline plasma soluble VEGFR1 (sVEGFR1) and hepatocyte growth factor (HGF) below median levels versus at or above the median levels (median OS [95% CI]: sVEGFR1, 11.2 [9.0-13.8] and 5.7 [4.3-7.0] months, respectively [P = .0002]; HGF, 11.2 [8.9-13.8] and 5.9 [5.0-7.6] months, respectively [P = 0.0002])., Conclusion: Dovitinib was well tolerated, but activity was not greater than sorafenib as a frontline systemic therapy for HCC. Based on these data, no subsequent phase 3 study has been planned. (Hepatology 2016;64:774-784)., (© 2016 by the American Association for the Study of Liver Diseases.)
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- 2016
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21. Hepatitis B virus full-length genomic mutations and quasispecies in hepatocellular carcinoma.
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Zhang AY, Lai CL, Poon RT, Huang FY, Seto WK, Fung J, Wong DK, and Yuen MF
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- Adult, Aged, Amino Acid Substitution, DNA, Viral analysis, DNA, Viral genetics, Female, Gene Deletion, Genome, Viral, Hepatitis B virus classification, Hepatitis B virus isolation & purification, Hepatitis B, Chronic complications, Humans, Liver virology, Male, Middle Aged, Mutagenesis, Insertional, Phylogeny, RNA, Viral analysis, Sequence Analysis, DNA, Carcinoma, Hepatocellular virology, Hepatitis B virus genetics, Hepatitis B, Chronic virology, Liver Neoplasms virology, Mutation
- Abstract
Background and Aim: Hepatitis B virus (HBV) full-length genomic mutations and quasispecies characteristics in hepatocellular carcinoma (HCC) were investigated., Methods: Hepatitis B virus DNA was extracted from the tumor and non-tumor tissues of 16 HCC patients. Overlapping DNA fragments covering the entire HBV genome were amplified and sequenced. To study HBV sequence at the quasispecies level, the preS region was amplified and clonally sequenced. HBV mutation profiles, quasispecies complexity and diversity, and phylogenetic characteristics were assessed., Results: Fourteen patients had full-length HBV amplification. Hot-spot mutations at HBx aa130-131 and pre-S deletions were detected in 13 (93%) and 6 (43%) patients, respectively. Deletions in the X/preC/C regions were more frequently detected in the tumor than in the non-tumor tissues (P = 0.031). Compared with the non-tumor tissues, the tumor tissues had a lower quasispecies complexity (P = 0.014 and 0.043, at the nucleotide and amino acid levels, respectively) and diversity (P = 0.048 and 0.022, at the nucleotide and amino acid levels, respectively). Phylogenetic analysis showed that HBV sequences derived from tumor and non-tumor tissues were separately clustered, suggesting the occurrence of compartmentalization, which was confirmed by the correlation coefficient testing on both the number and length of branches of viral populations (all P < 0.02)., Conclusions: Hepatitis B virus mutation patterns in HCC tumor tissues and non-tumor tissues were different. HBV quasispecies within the preS region were compartmentalized, and tumor tissues had a lower genome complexity and diversity. Our study suggests HBV evolution is conditioned by the differential host cellular environment in HCC tumors., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2016
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22. Integrative biomarker analyses indicate etiological variations in hepatocellular carcinoma.
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Zhu AX, Chen D, He W, Kanai M, Voi M, Chen LT, Daniele B, Furuse J, Kang YK, Poon RT, Vogel A, and Chiang DY
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- Biomarkers, Tumor, Humans, Proto-Oncogene Proteins c-met, Vascular Endothelial Growth Factor D, Carcinoma, Hepatocellular, Liver Neoplasms
- Abstract
Background & Aims: The purpose of this study was to determine whether biomarkers from baseline plasma and archival tissue specimens collected from patients enrolled in the EVOLVE-1 trial - a randomized phase 3 study of everolimus in hepatocellular carcinoma (HCC) - were associated with prognosis, etiology or ethnicity., Methods: Circulating plasma levels of bFGF, PLGF, VEGF, VEGF-D, c-Kit, collagen IV, sVEGFR1 and VEGFR2 were measured by ELISA (N=503). Protein levels of IGF-1R, c-Met, mTOR, Tsc2 were assayed by immunohistochemistry (N=125). Genomic DNA sequencing was conducted on a panel of 287 cancer-related genes (N=69)., Results: Patients with baseline plasma concentrations of VEGF or sVEGFR1 above the cohort median had significantly shorter overall survival. These plasma biomarkers retained prognostic significance in a multivariate Cox regression model with geographic region, macroscopic vascular invasion and alpha fetoprotein AFP levels. Membranous c-Met protein levels were significantly lower for Asian patients, as well as for hepatitis B viral etiology. The prevalence of genetic changes were similar to previous reports, along with a trend towards higher PTEN and TSC2 mutations among Asians., Conclusions: The angiogenesis biomarkers VEGF and sVEGFR1 were independent prognostic predictors of survival in patients with advanced HCC. Potential differences in c-Met and mTOR pathway activation between Asian and non-Asian patients should be considered in future clinical trials., Lay Summary: Our study demonstrates that circulating angiogenesis biomarkers can predict the survival outcome in patients with advanced hepatocellular carcinoma independent of the clinical variables. There is etiology and ethnicity variation in molecular pathway activation in hepatocellular carcinoma, which should be considered for future clinical trial design of targeted therapy., Clinical Trial Registration Number: NCT01035229., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
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- 2016
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23. Does hepatitis B seroconversion affect survival outcome in patients with hepatitis B related hepatocellular carcinoma?
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Yip VS, Cheung TT, Poon RT, Yau T, Fung J, Dai WC, Chan AC, Chok SH, Chan SC, and Lo CM
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Background: Little is known about whether hepatitis B surface antigen (HBsAg) seroconversion (SC) contributes to any survival benefits for patients with hepatocellular carcinoma (HCC)., Methods: All patients with hepatitis B-related HCC and HBsAg seroclearance between 1989 and 2013 were identified. Case- and control-groups were matched according to their stage of disease and mode of treatment. Baseline demographics, liver function, and overall survivals (OS) were compared between these two groups., Results: Thirty-nine HCC cases with HBsAg SC were identified, and 312 non-seroconversion (NSC) HCC cases were matched. Forty-eight percent of patients had curative resections, 14% were treated with ablation and 38% were for palliation. Age of patients in SC group was older than those in NSC group (P=0.026). Although there was significantly better liver function in SC vs . NSC groups in terms of bilirubin (P=0.027), albumin (P=0.003), AST (P=0.001) and ALT (P<0.001), there was no overall difference in Child-Pugh grade among the two groups. In regarding tumour pathology, SC commonly presented with solitary tumour nodule as compared to multiple nodules in NSC (P=0.027), and was also frequently associated with a normal background liver parenchyma (P<0.001). Although no survival benefit was confirmed in log-rank analysis between SC and NSC, the absolute 5-year survival of SC group was better in resection (72.2% vs . 55.3%), ablation (83.3% vs . 57.4%) and palliation (24.4% vs . 14.4%)., Conclusions: HCC patients with HBsAg SC are associated with a better background liver parenchyma and function, and might contribute to an improved long-term survival., Competing Interests: The authors have no conflicts of interest to declare.
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- 2016
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24. Corrigendum to "Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma" [J Hepatol 2015;62:607-616].
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Yeung OW, Lo CM, Ling CC, Qi X, Geng W, Li CX, Ng KT, Forbes SJ, Guan XY, Poon RT, Fan ST, and Man K
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- 2016
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25. Retrospective study of metachronous lung metastases from primary hepatocellular carcinoma.
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Chok KS, Yau TC, Cheung TT, Poon RT, and Lo CM
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- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Disease Management, Female, Humans, Liver Neoplasms mortality, Liver Neoplasms pathology, Lung Neoplasms mortality, Male, Middle Aged, Neoplasms, Second Primary mortality, Neoplasms, Second Primary therapy, Retrospective Studies, Survival Analysis, Treatment Outcome, Young Adult, Carcinoma, Hepatocellular surgery, Liver Neoplasms surgery, Lung Neoplasms secondary, Lung Neoplasms surgery, Neoplasms, Second Primary diagnosis
- Abstract
Background: This study investigates whether there has been any survival improvement for hepatocellular carcinoma patients with resectable and unresectable lung metastases over time., Methods: The data of 280 hepatocellular carcinoma patients who developed metachronous lung metastases after hepatectomy with curative intent were analysed. Overall survival was compared in patients with resectable and unresectable lung metastases and in different periods (Era I: 1989-1995, Era II: 1996-2010)., Results: The median overall survival of patients with unresectable and resectable diseases was 7.46 and 40.36 months, respectively (P < 0.0001). In Era I, the median overall survival of patients with unresectable and resectable diseases was 5.59 and 43.15 months, respectively (P < 0.0001). The corresponding figures in Era II were 8.38 and 32.90 months (P < 0.0001). The overall survival of patients with resectable disease did not differ significantly in the two eras but there was a significant improvement in survival of patients with unresectable disease in Era II. Their 1-year, 3-year and 5-year survival rates in Era I versus Era II were 11.1% versus 38.4%, 5.6% versus 9.1% and 2.8% versus 3.5%, respectively (P = 0.041). The corresponding figures for their counterparts in the resectable group were 90% versus 85.8%, 80% versus 45.9% and 40% versus 29.5%, respectively (P = 0.443)., Conclusions: Patients with resectable lung metastases had better overall survival than those with unresectable lung metastases. Notably, patients with unresectable lung metastases had significant improvement in survival over the years., (© 2014 Royal Australasian College of Surgeons.)
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- 2016
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26. Risk Factors and Post-Resection Independent Predictive Score for the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma.
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Hung IF, Wong DK, Poon RT, Fong DY, Chui AH, Seto WK, Fung JY, Chan AC, Yuen JC, Tiu R, Choi O, Lai CL, and Yuen MF
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- Aged, Antiviral Agents therapeutic use, Carcinoma, Hepatocellular surgery, DNA, Viral genetics, Female, Hepatitis B drug therapy, Hepatitis B virology, Hepatitis B virus pathogenicity, Humans, Liver Neoplasms surgery, Male, Middle Aged, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local surgery, Prospective Studies, Risk Factors, Carcinoma, Hepatocellular pathology, Hepatitis B complications, Liver Neoplasms pathology
- Abstract
Background: Independent risk factors associated with hepatitis B (HBV)-related hepatocellular carcinoma (HCC) after resection remains unknown. An accurate risk score for HCC recurrence is lacking., Methods: We prospectively followed up 200 patients who underwent liver resection for HBV-related HCC for at least 2 years. Demographic, biochemical, tumor, virological and anti-viral treatment factors were analyzed to identify independent risk factors associated with recurrence after resection and a risk score for HCC recurrence formulated., Results: Two hundred patients (80% male) who underwent liver resection for HBV-related HCC were recruited. The median time of recurrence was 184 weeks (IQR 52-207 weeks) for the entire cohort and 100 patients (50%) developed HCC recurrence. Stepwise Cox regression analysis identified that one-month post resection HBV DNA >20,000 IU/mL (p = 0.019; relative risk (RR) 1.67; 95% confidence interval (C.I.): 1.09-2.57), the presence of lymphovascular permeation (p<0.001; RR 2.69; 95% C.I.: 1.75-4.12), microsatellite lesions (p<0.001; RR 2.86; 95% C.I.: 1.82-4.51), and AFP >100ng/mL before resection (p = 0.021; RR 1.63; 95% C.I.: 1.08-2.47) were independently associated with HCC recurrence. Antiviral treatment before resection (p = 0.024; RR 0.1; 95% C.I.: 0.01-0.74) was independently associated with reduced risk of HCC recurrence. A post-resection independent predictive score (PRIPS) was derived and validated with sensitivity of 75.3% and 60.6% and specificity of 55.7% and 79.2%, to predict the 1- and 3-year risks for the HCC recurrence respectively with the hazard ratio of 2.71 (95% C.I.: 2.12-3.48; p<0.001). The AUC for the 1- and 3-year prediction were 0.675 (95% C.I.: 0.6-0.78) and 0.746 (95% C.I.: 0.69-0.82) respectively., Conclusion: Several tumor, virological and biochemical factors were associated with a higher cumulative risk of HCC recurrence after resection. PRIPS was derived for more accurate risk assessment. Regardless of the HBV DNA level, antiviral treatment should be given to patients before resection to reduce the risk of recurrence.
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- 2016
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27. Acute pancreatitis induced by transarterial chemoembolization: a single-center experience of over 1500 cases.
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She WH, Chan AC, Cheung TT, Chok KSh, Chan SC, Poon RT, and Lo CM
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- Acute Disease, Aged, Aged, 80 and over, Antineoplastic Agents administration & dosage, Cisplatin administration & dosage, Doxorubicin administration & dosage, Female, Hong Kong, Humans, Male, Middle Aged, Pancreatitis diagnosis, Pancreatitis therapy, Retrospective Studies, Time Factors, Treatment Outcome, Antineoplastic Agents adverse effects, Carcinoma, Hepatocellular therapy, Chemoembolization, Therapeutic adverse effects, Cisplatin adverse effects, Doxorubicin adverse effects, Liver Neoplasms therapy, Pancreatitis chemically induced
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Background: Acute pancreatitis is a relatively rare but potentially lethal complication after transarterial chemotherapy. This study aimed to review the complications such as acute pancreatitis after transarterial chemotherapy with or without embolization for hepatocellular carcinoma., Methods: A total of 1632 patients with hepatocellular carcinoma who had undergone transarterial chemoembolization from January 2000 to February 2014 in a single-center were reviewed retrospectively. We investigated the potential complications of transarterial chemoembolization, such as acute pancreatitis and acute pancreatitis-related complications., Results: Of the 1632 patients with hepatocellular carcinoma who had undergone 5434 transarterial chemoembolizations, 1328 were male and 304 female. The median age of these patients was 61 years. Most (79.6%) of the patients suffered from HBV-related hepatocellular carcinoma. The median tumor size was 5.2 cm. Of the 1632 patients, 145 patients underwent transarterial chemoembolization with doxorubicin eluting bead, making up a total of 538 episodes. The remaining patients underwent transarterial chemoembolization with cisplatin. Seven (0.4%) patients suffered from acute pancreatitis post-chemoembolization. Six patients had chemoembolization with doxorubicin and one had chemoembolization with cisplatin. Patients who received doxorubicin eluting bead had a higher risk of acute pancreatitis [6/145 (4.1%) vs 1/1487 (0.1%), P<0.0001]. Two patients had anatomical arterial variations. Four patients developed acute pancreatitis-related complications including necrotizing pancreatitis (n=3) and pseudocyst formation (n=1). All of the 4 patients resolved after the use of antibiotics and other conservative treatment. Three patients had further transarterial chemoembolization without any complication., Conclusions: Acute pancreatitis after transarterial chemoembolization could result in serious complications, especially after treatment with doxorubicin eluting bead. Continuation of current treatment with transarterial chemoembolization after acute pancreatitis is feasible providing the initial attack is completely resolved.
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- 2016
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28. Safety of ALPPS Procedure by the Anterior Approach for Hepatocellular Carcinoma.
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Chan AC, Poon RT, Chan C, and Lo CM
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- Aged, Aged, 80 and over, Female, Humans, Ligation, Male, Middle Aged, Patient Safety, Portal Vein surgery, Treatment Outcome, Carcinoma, Hepatocellular surgery, Hepatectomy methods, Liver Neoplasms surgery
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- 2016
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29. Pure Laparoscopic Versus Open Left Lateral Sectionectomy for Hepatocellular Carcinoma: A Single-Center Experience.
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Cheung TT, Poon RT, Dai WC, Chok KS, Chan SC, and Lo CM
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- Adult, Aged, Aged, 80 and over, Blood Loss, Surgical, Female, Humans, Laparoscopy methods, Length of Stay statistics & numerical data, Liver Cirrhosis surgery, Male, Middle Aged, Operative Time, Retrospective Studies, Treatment Outcome, Carcinoma, Hepatocellular surgery, Hepatectomy methods, Liver Neoplasms surgery
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Introduction: Laparoscopic left lateral sectionectomy has been proven to be a safe and effective treatment for liver lesions. However, most of the literatures only reported this treatment method on benign lesion or colorectal metastases. The data on long-term outcome of laparoscopic left lateral section resection in patients with HCC and cirrhosis are still limited. The aim of this study is to analyze the survival outcome of laparoscopic left lateral sectionectomy when compared to open approach in patients with HCCs., Method: Between January 2004 and September 2014, 967 patients had primary HCC with hepatectomy performed. Twenty-four patients had undergone pure laparoscopic left lateral sectionectomy for hepatocellular carcinoma (HCC). Twenty-nine patients with case-matched tumor characteristics and liver functions but received open left lateral sectionectomy for HCC were included for comparison., Results: Comparing laparoscopic group to open resection group, the median operation time was 190.5 versus 195 min (P = 0.734); the median blood loss was 100 versus 300 ml (P < 0.001). Hospital stay was 5 days in laparoscopic group versus 6 days in the open group (P = 0.057). There was no difference between the two groups in terms of complications (P = 0.495). The median survival in laparoscopic group was >115 months versus >125 months in the open group (P = 0.853)., Conclusion: Laparoscopic left lateral sectionectomy for HCC is a safe and simple procedure associated with less blood loss. The survival outcome is comparable with conventional open approach. It is becoming a more favorable treatment option even for patients with HCC and cirrhosis.
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- 2016
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30. Efficacy of radiofrequency ablation compared with transarterial chemoembolization for the treatment of recurrent hepatocellular carcinoma: a comparative survival analysis.
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Koh PS, Chan AC, Cheung TT, Chok KS, Dai WC, Poon RT, and Lo CM
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- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Catheter Ablation adverse effects, Catheter Ablation mortality, Chi-Square Distribution, Databases, Factual, Female, Humans, Kaplan-Meier Estimate, Liver Neoplasms mortality, Liver Neoplasms pathology, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Reoperation, Retrospective Studies, Risk Factors, Salvage Therapy, Time Factors, Treatment Outcome, Tumor Burden, Carcinoma, Hepatocellular therapy, Chemoembolization, Therapeutic adverse effects, Chemoembolization, Therapeutic mortality, Hepatectomy adverse effects, Hepatectomy mortality, Liver Neoplasms therapy, Neoplasm Recurrence, Local
- Abstract
Background: This study aims to assess if radiofrequency ablation (RFA) has any oncological superiority over transarterial chemoembolization (TACE) on post-hepatectomy recurrence., Methodology: From 2002 to 2011, 60.15% of 823 patients developed recurrence after hepatectomy for Hepatocellular carcinoma (HCC). 102 patients with recurrence underwent RFA (n = 42) or TACE (n = 60) for tumor size ≤5 cm and number of lesion ≤3 when tumors were not resectable or transplantable. Those with renal impairment, portal vein thrombosis and poor liver reserve were excluded. Primary outcome was overall survival, which was determined using log-rank test and Kaplan Meier plots performed. Categorical data were analyzed using Chi-square test and continuous variable were analyzed using Mann-U Whitney test., Results: Demographics and primary tumor characteristics were similar in both groups (p > 0.05). Overall survival after initial hepatectomy and salvage treatment for recurrence was similar (p > 0.05) in both groups with 5-year OS after salvage treatment for RFA and TACE at 24.1% and 25.7%, respectively. For patients with second recurrence after salvage treatment, an interchangeable treatment strategy of RFA and TACE conferred a better survival outcome than a stand-alone treatment with RFA or TACE (p < 0.05)., Conclusions: RFA and TACE may be equally effective for intrahepatic recurrence after hepatectomy when tumor size is ≤5 cm and ≤3 lesion when re-resection or salvage transplantation is not considered feasible., (Copyright © 2015 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)
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- 2016
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31. Comparison of Survival Outcomes Between Right Posterior Sectionectomy and Right Hepatectomy for Hepatocellular Carcinoma in Cirrhotic Liver: A Single-Centre Experience.
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Yip VS, Poon RT, Chok KS, Chan AC, Dai WC, Tsang SH, Chan SC, Lo CM, and Cheung TT
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- Adult, Aged, Carcinoma, Hepatocellular complications, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Disease-Free Survival, Female, Hepatectomy mortality, Hepatic Veins surgery, Hepatitis B, Chronic complications, Humans, Liver Cirrhosis complications, Liver Failure, Liver Neoplasms complications, Liver Neoplasms mortality, Liver Neoplasms pathology, Male, Middle Aged, Postoperative Period, Survival Rate, Tumor Burden, Carcinoma, Hepatocellular surgery, Hepatectomy methods, Liver Neoplasms surgery
- Abstract
Background: Right hepatectomy (RH) instead of right posterior sectionectomy (RPS) is commonly performed for hepatocellular carcinoma (HCC) in cirrhotic livers located lateral to the right hepatic vein in order to ensure adequate resection margin. This potentially increased the risk of postoperative liver failure. This study aims to compare survival outcomes and surgical morbidities between RH and RPS., Methods: All patients between 2003 and 2013 with resection for solitary HCC in cirrhotic livers at segment 6/7 were reviewed. Baseline demographics, liver function, perioperative outcomes, and overall (OS) and disease-free survival (DFS) were compared between RH and RPS., Results: Eighty-one patients were included in this study. Thirty-two patients had RH and forty-nine with RPS were selected as controls. Majority of the HCC patients (91.4 %) suffered from chronic hepatitis B. There was no significant difference in age, gender and Child-Pugh grade between the two groups. The median tumour size of RH group was 6 vs. 4 cm in the RPS group (p < 0.0001). Both groups had no statistical difference in resection margin and their associated morbidities. The 5-year OS for RH and RPS was 76 and 83.8 %, respectively (p = 0.766), whereas their corresponding DFS was 52.6 and 52.2 % (p = 0.859). Despite the discrepancy of tumour size among the two groups, there was no statistical difference in subgroup analysis based on their corresponding stage of disease., Conclusion: RPS can achieve similar OS and DFS as RH for HCC, and should be considered as the treatment of choice in order to optimise the postoperative remnant parenchymal liver functions.
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- 2015
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32. Modified Anterior Approach for the ALPPS Procedure: How We Do It.
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Chan AC, Poon RT, and Lo CM
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- Aged, Aged, 80 and over, Carcinoma, Hepatocellular pathology, Female, Humans, Hypertrophy pathology, Ligation, Liver Neoplasms pathology, Liver Regeneration, Male, Middle Aged, Organ Size, Portal Vein surgery, Retrospective Studies, Tumor Burden, Vascular Surgical Procedures, Carcinoma, Hepatocellular surgery, Hepatectomy methods, Liver pathology, Liver Neoplasms surgery
- Abstract
Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a highly complex operation that demands a thorough understanding of the intrahepatic vascular anatomy and skills in parenchymal transection for the in situ split procedure. In order to minimize adhesion formation after the stage I operation and to avoid iatrogenic tumor rupture during right liver mobilization in large tumors, anterior approach appears to be a logical approach for the in situ split procedure. However, in contrast to the anterior approach adopted for the usual right hepatectomy, the right hepatic artery and biliary pedicle remain intact and undivided during the first operation. To address this issue, we hereby reported our experience of the modified 'anterior approach' for the ALPPS procedure that facilitates a complete in situ parenchymal split., Methods: Prospectively collected data of 13 patients who underwent the ALPPS procedure by the modified anterior approach for hepatocellular carcinoma from October 2013 to October 2014 were reviewed., Results: The baseline future liver remnant volume (FLR) was 286 ml. The median tumor size was 6.0 cm. After a median of 8 days from stage I operation, the left FLR hypertrophied by 52.7 % in volume to 482 ml. All patients proceeded to second stage hepatectomy (extended right hepatectomy, n = 5; right hepatectomy, n = 6; right trisectionectomy, n = 2) without significant adhesion encountered. The overall morbidity and mortality rates were 7.7 % (n = 1) and 7.7 % (n = 1), respectively., Conclusion: The modified anterior approach is safe and feasible for complete in situ split in the ALPPS procedure.
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- 2015
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33. Defining an optimal surgical strategy for synchronous colorectal liver metastases: staged versus simultaneous resection?
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She WH, Chan AC, Poon RT, Cheung TT, Chok KS, Chan SC, and Lo CM
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- Adult, Aged, Aged, 80 and over, Colorectal Neoplasms mortality, Female, Follow-Up Studies, Humans, Length of Stay, Liver Neoplasms mortality, Male, Middle Aged, Retrospective Studies, Survival Analysis, Time Factors, Colectomy, Colorectal Neoplasms pathology, Colorectal Neoplasms surgery, Hepatectomy, Liver Neoplasms secondary, Liver Neoplasms surgery
- Abstract
Background: We aimed to assess if simultaneous resection conferred any survival benefit in resection of synchronous colorectal liver metastases., Methods: From January 1990 to December 2008, 116 patients with synchronous colorectal liver metastases were identified. Among these 116 patients, 88 underwent staged resection (SR), while the remaining 28 patients underwent simultaneous resection (SIMR). Patients' follow-up data were reviewed., Results: There were no significant differences between the groups in terms of patient and tumour characteristics. Major hepatectomy was performed in 54 patients (61%) undergoing SR, and 12 patients (43%) undergoing SIMR (P = 0.09). The median blood loss (SR 0.7 L versus SIMR 0.8 L) was similar. Post-operative morbidity rates and hospital mortality rates were not statistically different. The total length of hospital stay was shorter in SIMR patients (18.0 versus 11.5 days, P = 0.009). The 1-, 3- and 5-year overall survival for SR were 90.7%, 47.1% and 33.3%, whilst the corresponding survival rates for SIMR were 75.0%, 25.0% and 0%, respectively (P = 0.003). However, when the disease-free survival (DFS) was stratified according to the number of hepatic metastases, the survival benefit of SR and SIMR for solitary CRM were similar (3-year DFS: 28.3% versus 11.1%, P = 0.089)., Conclusions: Our study showed that an operative strategy of SR generally offered better survival outcome than SIMR in the surgical management of CRM., (© 2014 Royal Australasian College of Surgeons.)
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- 2015
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34. Efficacy of radiofrequency ablation compared with transarterial chemoembolization for the treatment of recurrent hepatocellular carcinoma: a comparative survival analysis.
- Author
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Koh PS, Chan AC, Cheung TT, Chok KS, Dai WC, Poon RT, and Lo CM
- Abstract
Background: This study aims to assess if radiofrequency ablation (RFA) has any oncological superiority over transarterial chemoembolization(TACE) on post-hepatectomy recurrence., Methods: From 2002 to 2011, 60.15% of 823 patients developed recurrence after hepatectomy for HCC. One hundred and two patients with recurrence underwent RFA (n = 42) or TACE (n = 60) for tumour size ≤5 cm and number of lesions ≤ 3 when tumours were not resectable or transplantable. Those with renal impairment, portal vein thrombosis and poor liver reserve were excluded. The primary outcome was overall survival, which was determined using log-rank test and Kaplan-Meier plots performed. Categorical data were analysed using the chi-square test and continuous variable were analysed using the Mann-Whitney U-test., Results: Demographics and primary tumour characteristics were similar in both groups (P > 0.05). Overall survival (OS) after an initial hepatectomy and salvage treatment for recurrence was similar (P > 0.05) in both groups with a 5-year OS after salvage treatment for RFA and TACE at 24.1% and 25.7%, respectively. For patients with the second recurrence after salvage treatment, an interchangeable treatment strategy of RFA and TACE conferred a better survival outcome than a stand-alone treatment with RFA or TACE (P < 0.05)., Conclusions: RFA and TACE may be equally effective for intrahepatic recurrence after hepatectomy when the tumour size is ≤ 5 cm and ≤ 3 lesions when re-resection or salvage transplantation is not considered feasible., (© 2015 International Hepato-Pancreato-Biliary Association.)
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- 2015
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35. Quality of life changes in patients undergoing treatment for hepatocellular carcinoma.
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Chie WC, Yu F, Li M, Baccaglini L, Blazeby JM, Hsiao CF, Chiu HC, Poon RT, Mikoshiba N, Al-Kadhimi G, Heaton N, Calara J, Collins P, Caddick K, Costantini A, Vilgrain V, and Chiang C
- Subjects
- Carcinoma, Hepatocellular pathology, Female, Humans, Liver Neoplasms pathology, Longitudinal Studies, Male, Middle Aged, Quality of Life, Surveys and Questionnaires, Carcinoma, Hepatocellular epidemiology, Liver Neoplasms epidemiology
- Abstract
Purpose: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. One of the primary treatment goals for incurable advanced cases is to prolong quality of life (QoL). Thus, to determine which HCC therapies may be linked to a more favorable QoL, we assessed the association between QoL changes and different treatments in HCC patients., Methods: We analyzed a non-randomized multicenter longitudinal study, which included 171 patients treated with surgery (n = 53), ablation (n = 53) or embolization (n = 65) from seven centers: four Asian and three European sites. All participants completed the EORTC QLQ-C30 and QLQ-HCC18 questionnaires before and after treatment. Propensity scores were calculated and used in addition to race for adjustment in the logistic regression model to account for the confounding effects of patient characteristics including age, gender, race, employment, living with family, at least one comorbid condition, years since diagnosis, prior treatment history, BCLC stage, Child-Pugh grade, cirrhosis, bilirubin levels and QoL score before treatment., Results: After adjustment for confounders, patients tended to have higher odds of QoL deterioration when treated with ablation versus embolization (dyspnea: p = 0.019; appetite loss: p = 0.018; body image: p = 0.035) or ablation versus surgery (dyspnea: p = 0.099; appetite loss: p = 0.100; body image: p = 0.038)., Conclusions: There were significant differences in QoL deterioration across different treatment groups. This information may assist patients and providers when selecting patient-centered treatment approaches for HCC.
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- 2015
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36. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial.
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Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, Cai J, Poon RT, Han KH, Tak WY, Lee HC, Song T, Roayaie S, Bolondi L, Lee KS, Makuuchi M, Souza F, Berre MA, Meinhardt G, and Llovet JM
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Asia, Australia, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Chemotherapy, Adjuvant, Disease Progression, Disease-Free Survival, Double-Blind Method, Europe, Female, Humans, Intention to Treat Analysis, Kaplan-Meier Estimate, Liver Neoplasms mortality, Liver Neoplasms pathology, Male, Middle Aged, Neoplasm Recurrence, Local, New Zealand, Niacinamide administration & dosage, Niacinamide adverse effects, Niacinamide therapeutic use, North America, Phenylurea Compounds administration & dosage, Phenylurea Compounds adverse effects, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Risk Factors, Sorafenib, South America, Time Factors, Treatment Outcome, Young Adult, Antineoplastic Agents therapeutic use, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular surgery, Catheter Ablation adverse effects, Catheter Ablation mortality, Hepatectomy adverse effects, Hepatectomy mortality, Liver Neoplasms drug therapy, Liver Neoplasms surgery, Niacinamide analogs & derivatives, Phenylurea Compounds therapeutic use, Protein Kinase Inhibitors therapeutic use
- Abstract
Background: There is no standard of care for adjuvant therapy for patients with hepatocellular carcinoma. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation., Methods: We undertook this phase 3, double-blind, placebo-controlled study of patients with hepatocellular carcinoma with a complete radiological response after surgical resection (n=900) or local ablation (n=214) in 202 sites (hospitals and research centres) in 28 countries. Patients were randomly assigned (1:1) to receive 400 mg oral sorafenib or placebo twice a day, for a maximum of 4 years, according to a block randomisation scheme (block size of four) using an interactive voice-response system. Patients were stratified by curative treatment, geography, Child-Pugh status, and recurrence risk. The primary outcome was recurrence-free survival assessed after database cut-off on Nov 29, 2013. We analysed efficacy in the intention-to-treat population and safety in randomly assigned patients receiving at least one study dose. The final analysis is reported. This study is registered with ClinicalTrials.gov, number NCT00692770., Findings: We screened 1602 patients between Aug 15, 2008, and Nov 17, 2010, and randomly assigned 1114 patients. Of 556 patients in the sorafenib group, 553 (>99%) received the study treatment and 471 (85%) terminated treatment. Of 558 patients in the placebo group, 554 (99%) received the study treatment and 447 (80%) terminated treatment. Median duration of treatment and mean daily dose were 12·5 months (IQR 2·6-35·8) and 577 mg per day (SD 212·8) for sorafenib, compared with 22·2 months (8·1-38·8) and 778·0 mg per day (79·8) for placebo. Dose modification was reported for 497 (89%) of 559 patients in the sorafenib group and 206 (38%) of 548 patients in the placebo group. At final analysis, 464 recurrence-free survival events had occurred (270 in the placebo group and 194 in the sorafenib group). Median follow-up for recurrence-free survival was 8·5 months (IQR 2·9-19·5) in the sorafenib group and 8·4 months (2·9-19·8) in the placebo group. We noted no difference in median recurrence-free survival between the two groups (33·3 months in the sorafenib group vs 33·7 months in the placebo group; hazard ratio [HR] 0·940; 95% CI 0·780-1·134; one-sided p=0·26). The most common grade 3 or 4 adverse events were hand-foot skin reaction (154 [28%] of 559 patients in the sorafenib group vs four [<1%] of 548 patients in the placebo group) and diarrhoea (36 [6%] vs five [<1%] in the placebo group). Sorafenib-related serious adverse events included hand-foot skin reaction (ten [2%]), abnormal hepatic function (four [<1%]), and fatigue (three [<1%]). There were four (<1%) drug-related deaths in the sorafenib group and two (<1%) in the placebo group., Interpretation: Our data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
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- 2015
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37. A preclinical study on the combination therapy of everolimus and transarterial chemoembolization in hepatocellular carcinoma.
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Chow AK, Yau TC, Ng L, Chu AC, Law WL, Poon RT, and Pang RW
- Abstract
Transarterial chemoembolization (TACE) is commonly used for the treatment of locally advanced hepatocellular carcinoma (HCC) by its dual effects of chemotherapy and ischemic hypoxia. However, one of the side effects of TACE is the introduction of hypoxic condition, which in turn activates hypoxia-induced survival pathways and enhances VEGF-induced neovascularization by stabilizing HIF-1α expression. Herein, the preclinical therapeutic efficacy of the combined treatment of everolimus, a novel mTOR inhibitor and TACE for the treatment of HCC was investigated. The MHCC-97L cells were used for the study of the effect of combined treatment on cell proliferation and cellular apoptosis. HUVEC cells were used for the study on tube formation under different treatments. Inhibitions on the Akt/mTOR pathways were also studied. Finally, the effect on tumor growth was further study using an in vivo orthotopic model. The results demonstrated that everolimus enhanced the therapeutic efficacy of TACE in inhibiting cell proliferation, promoting apoptosis and inhibiting tube formation of endothelial cells by blocking the Akt/mTOR signaling pathway in vitro and inhibiting tumor growth and neoangiogenesis in vivo. Based on this preclinical study, the potential of combining everolimus with TACE was guaranteed which suggested the use of the combination therapy in the clinical treatment of advanced HCC patients.
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- 2015
38. Reply to Letter: "Long-term Survival Analysis of Pure Laparoscopic Versus Open Hepatectomy for Hepatocellular Carcinoma in Patients With Cirrhosis: A Single-center Experience".
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Cheung TT, Poon RT, and Lo CM
- Subjects
- Female, Humans, Male, Carcinoma, Hepatocellular mortality, Hepatectomy methods, Laparoscopy, Liver Cirrhosis complications, Liver Neoplasms mortality
- Published
- 2015
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39. Technical considerations for ligation of ruptured hepatic artery aneurysm: is arterial reconstruction necessary?
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Lam S, Chan AC, and Poon RT
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- Aged, Aneurysm, Ruptured diagnostic imaging, Hepatic Artery diagnostic imaging, Humans, Ligation methods, Liver diagnostic imaging, Male, Radiography, Ultrasonography, Aneurysm, Ruptured surgery, Hepatic Artery surgery, Liver blood supply
- Abstract
Ruptured hepatic artery aneurysm is a rare life-threatening condition. Open surgery with ligation of the aneurysm is the treatment of choice if the patient presents with haemodynamic instability. Controversies exist on whether hepatic artery reconstruction is needed after exclusion of the aneurysm. Involvement of the gastroduodenal artery origin was proposed as an indication for reconstruction, but this might be difficult to ascertain upon laparotomy. Recent studies showed that arterial ligation distal to the gastroduodenal artery origin does not necessarily result in ischaemic liver injury, implying that reconstruction in such cases may not be required, especially in a haemodynamically unstable patient. A patient with common hepatic artery aneurysm involving the gastroduodenal artery origin presented with rupture and underwent aneurysm ligation. Adequacy of intrahepatic arterial flow was determined by intra-operative Doppler ultrasonography and arterial reconstruction was not performed. The technical considerations during the operative management of ruptured hepatic artery aneurysms are discussed.
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- 2015
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40. Post-operative plasma osteopontin predicts distant metastasis in human colorectal cancer.
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Ng L, Wan TM, Lam CS, Chow AK, Wong SK, Man JH, Li HS, Cheng NS, Pak RC, Cheung AH, Yau TC, Lo OS, Foo DC, Poon JT, Poon RT, Pang RW, and Law WL
- Subjects
- Cell Line, Tumor, Colorectal Neoplasms complications, Colorectal Neoplasms surgery, Enzyme-Linked Immunosorbent Assay, Humans, Neoplasm Metastasis, Postoperative Period, Biomarkers, Tumor blood, Colorectal Neoplasms blood, Colorectal Neoplasms pathology, Osteopontin blood
- Abstract
Background: The overall prognosis of colorectal cancer (CRC) patients is unsatisfactory due to cancer metastasis after operation. This study aims to investigate the clinical significance of plasma osteopontin (OPN) levels as minimally invasive, predictive, and surrogate biomarkers for prognosis of CRC patients., Methods: This randomized study design consists of pre-operative and post-operative plasma samples from a total of 79 patients. We determined plasma levels of OPN by ELISA and examined their correlation with the clinicopathological parameters of CRC patients. The effects of endogenous and exogenous OPN on CRC metastasis were investigated by examination of the effect on regulators of epithelial to messenchymal transition and migration assay., Results: Our findings demonstrated for the first time the clinical correlation of plasma OPN with metastasis of CRC patients. High post-operative plasma OPN level (>153.02 ng/ml) associated with development of metastasis after curative resection (p<0.001). Moreover, post-operative plasma OPN level correlated with disease-free survival of CRC patients (p=0.009) and was an independent factor for predicting development of metastasis in CRC patients after curative resection (p=0.036). Our in vitro model showed that OPN ectopic expression induced DLD1 cell migration through Snail and Twist1 overexpression and E-cadherin repression, and secretory OPN level enhanced cell migration., Conclusions: The results of the current study suggest that post-operative plasma OPN correlated with post-operative metastasis, suggesting that it is a potential non-invasive biomarker for the development of future metastasis in CRC patients. In addition, OPN was shown to be involved in the metastatic process and thus inhibition of OPN is a potential therapeutic approach to treat CRC patients.
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- 2015
- Full Text
- View/download PDF
41. Outcomes of hepatectomy for hepatocellular carcinoma with bile duct tumour thrombus.
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Wong TC, Cheung TT, Chok KS, Chan AC, Dai WC, Chan SC, Poon RT, Fan ST, and Lo CM
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular complications, Carcinoma, Hepatocellular diagnosis, Female, Follow-Up Studies, Humans, Liver Neoplasms complications, Liver Neoplasms diagnosis, Male, Middle Aged, Retrospective Studies, Thrombosis diagnosis, Thrombosis etiology, Young Adult, Bile Ducts surgery, Carcinoma, Hepatocellular surgery, Hepatectomy methods, Liver Neoplasms surgery, Thrombosis surgery
- Abstract
Background: Hepatocellular carcinoma (HCC) with bile duct tumour thrombus (BDTT) is rare. The aim of the present study was to determine the prognosis of HCC with BDTT after a hepatectomy., Methods: A retrospective analysis was performed on all HCC patients with BDTT having a hepatectomy from 1989 to 2012. The outcomes in these patients were compared with those in the control patients matched on a 1:6 ratio., Results: Thirty-seven HCC patients with BDTT having a hepatectomy (the BDTT group) were compared with 222 control patients. Patients in the BDTT group had poorer liver function (43.2% had Child-Pugh B disease). More patients in this group had a major hepatectomy (91.9% versus 27.5%, P = 0.001), portal vein resection (10.8% versus 1.4%, P = 0.006), en-bloc resection with adjacent structures (16.2% versus 5.4%, P = 0.041), hepaticojejunostomy (75.7% versus 1.6%, P < 0.001) and complications (51.4% versus 31.1%, P = 0.016). The two groups had similar hospital mortality (2.7% versus 5.0%, P = 0.856), 5-year overall survival (38.5% versus 34.6%, P = 0.59) and 5-year disease-free survival (21.1% versus 20.8%, P = 0.81). Multivariate analysis showed that lymphovascular permeation, tumour size and post-operative complication were significant predictors for worse survival whereas BDTT was not., Discussion: A major hepatectomy, extrahepatic biliary resection and hepaticojejunostomy should be the standard for HCC with BDTT, and long-term survival is possible after radical surgery., (© 2014 International Hepato-Pancreato-Biliary Association.)
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- 2015
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42. Copy number gain of granulin-epithelin precursor (GEP) at chromosome 17q21 associates with overexpression in human liver cancer.
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Yung MK, Lo KW, Yip CW, Chung GT, Tong CY, Cheung PF, Cheung TT, Poon RT, So S, Fan ST, and Cheung ST
- Subjects
- Aged, Carcinoma, Hepatocellular pathology, Chromosomes, Human, Pair 17 genetics, Female, Gene Expression Regulation, Neoplastic, Humans, In Situ Hybridization, Fluorescence, Intercellular Signaling Peptides and Proteins biosynthesis, Liver Neoplasms pathology, Male, Microsatellite Repeats genetics, Middle Aged, Neoplasm Staging, Progranulins, Carcinoma, Hepatocellular genetics, Gene Dosage genetics, Intercellular Signaling Peptides and Proteins genetics, Liver Neoplasms genetics
- Abstract
Background: Granulin-epithelin precursor (GEP), a secretory growth factor, demonstrated overexpression in various human cancers, however, mechanism remain elusive. Primary liver cancer, hepatocellular carcinoma (HCC), ranks the second in cancer-related death globally. GEP controlled growth, invasion, metastasis and chemo-resistance in liver cancer. Noted that GEP gene locates at 17q21 and the region has been frequently reported to be amplified in subset of HCC. The study aims to investigate if copy number gain would associate with GEP overexpression., Methods: Quantitative Microsatellite Analysis (QuMA) was used to quantify the GEP DNA copy number, and fluorescent in situ hybridization (FISH) was performed to consolidate the amplification status. GEP gene copy number, mRNA expression level and clinico-pathological features were analyzed., Results: GEP DNA copy number determined by QuMA corroborated well with the FISH data, and the gene copy number correlated with the expression levels (n = 60, r = 0.331, P = 0.010). Gain of GEP copy number was observed in 20% (12/60) HCC and associated with hepatitis B virus infection status (P = 0.015). In HCC with increased GEP copy number, tight association between GEP DNA and mRNA levels were observed (n = 12, r = 0.664, P = 0.019)., Conclusions: Gain of the GEP gene copy number was observed in 20% HCC and the frequency comparable to literatures reported on the chromosome region 17q. Increased gene copy number contributed to GEP overexpression in subset of HCC.
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- 2015
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43. Preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and quality of life study of pegylated recombinant human arginase 1 in patients with advanced hepatocellular carcinoma.
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Yau T, Cheng PN, Chan P, Chen L, Yuen J, Pang R, Fan ST, Wheatley DN, and Poon RT
- Subjects
- Adult, Aged, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols, Area Under Curve, Arginase administration & dosage, Arginase adverse effects, Arginase pharmacokinetics, Chemistry, Pharmaceutical, Disease-Free Survival, Dose-Response Relationship, Drug, Female, Half-Life, Humans, Male, Metabolic Clearance Rate, Middle Aged, Prospective Studies, Recombinant Proteins, Response Evaluation Criteria in Solid Tumors, Antineoplastic Agents pharmacology, Arginase pharmacology, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Polyethylene Glycols chemistry, Quality of Life
- Abstract
This study was designed to evaluate the efficacy, safety profile, pharmacokinetics, pharmacodynamics and quality of life of pegylated recombinant human arginase 1 (Peg-rhAgr1) in patients with advanced hepatocellular carcinoma (HCC). Patients were given weekly doses of Peg-rhAgr1 (1600 U/kg). Tumour response was assessed every 8 weeks using RECIST 1.1 and modified RECIST criteria. A total of 20 patients were recruited, of whom 15 were deemed evaluable for treatment efficacy. Eighteen patients (90%) were hepatitis B carriers. Median age was 61.5 (range 30-75). Overall disease control rate was 13%, with 2 of the 15 patients achieving stable disease for >8 weeks. The median progression-free survival (PFS) was 1.7 (95% CI: 1.67-1.73) months, with median overall survival (OS) of all 20 enrolled patients being 5.2 (95% CI: 3.3-12.0) months. PFS was significantly prolonged in patients with adequate arginine depletion (ADD) >2 months versus those who had ≤2 months of ADD (6.4 versus 1.7 months; p = 0.01). The majority of adverse events (AEs) were grade 1/2 non-hematological toxicities. Transient liver dysfunctions (25%) were the most commonly reported serious AEs and likely due to disease progression. Pharmacokinetic and pharmacodynamic data showed that Peg-rhAgr1 induced rapid and sustained arginine depletion. The overall quality of life of the enrolled patients was well preserved. Peg-rhAgr1 is well tolerated with a good toxicity profile in patients with advanced HCC. A weekly dose of 1600 U/kg is sufficient to induce ADD. Significantly longer PFS times were recorded for patients who had ADD for >2 months.
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- 2015
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44. Radiofrequency ablation versus transarterial chemoembolization for unresectable solitary hepatocellular carcinomas sized 5-8 cm.
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Dai WC, Cheung TT, Chok KS, Chan AC, Sharr WW, Tsang SH, Yuen WK, Chan SC, Fan ST, Lo CM, and Poon RT
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular therapy, Catheter Ablation adverse effects, Chemoembolization, Therapeutic adverse effects, Chi-Square Distribution, Cohort Studies, Disease-Free Survival, Female, Humans, Infusions, Intra-Arterial, Kaplan-Meier Estimate, Liver Neoplasms mortality, Liver Neoplasms therapy, Male, Middle Aged, Neoplasm Invasiveness pathology, Neoplasm Staging, Prognosis, Retrospective Studies, Risk Assessment, Statistics, Nonparametric, Survival Analysis, Treatment Outcome, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular surgery, Catheter Ablation methods, Chemoembolization, Therapeutic methods, Liver Neoplasms pathology, Liver Neoplasms surgery
- Abstract
Objectives: This retrospective review was conducted to compare the efficacy of radiofrequency ablation (RFA) with that of transarterial chemoembolization (TACE) in treating large (5-8 cm) unresectable solitary hepatocellular carcinomas (HCCs)., Methods: Patients with large unresectable solitary HCCs primarily treated by RFA or TACE were reviewed. The primary endpoint was overall survival. Secondary endpoints were tumour response, time to disease progression, and treatment-related morbidity and mortality., Results: There were 15 patients in the RFA group. Of these, 12 achieved complete ablation, one had ablation site recurrence, and five developed complications. Median disease-free survival in this group was 13.0 months (range: 2.8-38.0 months). The TACE group included 26 patients, of whom four obtained a partial response, none achieved a complete response, and five developed complications. The median time to disease progression in this group was 8.0 months (range: 1.0-68.0 months). There were no hospital deaths in this series. Median survival was 39.8 months in the RFA group and 19.8 months in the TACE group (P = 0.257). Rates of 1-, 2- and 5-year survival were 93.3%, 86.2% and 20.9%, respectively, in the RFA group and 73.1%, 40.6% and 18.3%, respectively, in the TACE group., Conclusions: Both RFA and TACE are feasible treatments for large unresectable solitary HCCs. Both modes show comparable rates of complications and longterm survival, but RFA achieves better initial tumour control and results in better short-term survival., (© 2014 International Hepato-Pancreato-Biliary Association.)
- Published
- 2015
- Full Text
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45. Hong Kong consensus recommendations on the management of hepatocellular carcinoma.
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Poon RT, Cheung TT, Kwok PC, Lee AS, Li TW, Loke KL, Chan SL, Cheung MT, Lai TW, Cheung CC, Cheung FY, Loo CK, But YK, Hsu SJ, Yu SC, and Yau T
- Abstract
Background: Hepatocellular carcinoma (HCC) is particularly prevalent in Hong Kong because of the high prevalence of chronic hepatitis B (CHB) infection; HCC is the fourth commonest cancer in men and the seventh commonest in women, and it is the third leading cause of cancer death in Hong Kong. The full spectrum of treatment modalities for HCC is available locally; however, there is currently no local consensus document detailing how these modalities should be used., Summary: In a series of meetings held between May and October 2013, a multidisciplinary group of Hong Kong clinicians - liver surgeons, medical oncologists, clinical oncologists, hepatologists, and interventional radiologists - convened to formulate local recommendations on HCC management. These recommendations consolidate the most current evidence pertaining to HCC treatment modalities, together with the latest thinking of practicing clinicians engaged in HCC management, and give detailed guidance on how to deploy these modalities effectively for patients in various disease stages., Key Messages: Distinct from other regional guidelines, these recommendations provide guidance on the use of antiviral therapy to reduce the incidence of HCC in CHB patients with cirrhosis and to reduce recurrence of CHB-related HCC.
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- 2015
- Full Text
- View/download PDF
46. Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma.
- Author
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Yeung OW, Lo CM, Ling CC, Qi X, Geng W, Li CX, Ng KT, Forbes SJ, Guan XY, Poon RT, Fan ST, and Man K
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Antigens, CD metabolism, Antigens, Differentiation, Myelomonocytic metabolism, Carcinoma, Hepatocellular secondary, Cell Line, Cell Line, Tumor, Cell Proliferation, Chemokine CCL22 metabolism, Coculture Techniques, Epithelial-Mesenchymal Transition immunology, Female, Heterografts, Humans, Macrophage Activation, Macrophages classification, Male, Mice, Inbred BALB C, Mice, Nude, Middle Aged, Neoplasm Invasiveness immunology, Neoplasm Invasiveness pathology, Prognosis, Receptors, CCR4 metabolism, Receptors, Cell Surface metabolism, Scavenger Receptors, Class A metabolism, Young Adult, Carcinoma, Hepatocellular immunology, Carcinoma, Hepatocellular pathology, Liver Neoplasms immunology, Liver Neoplasms pathology, Macrophages immunology
- Abstract
Background & Aims: The roles of alternatively activated (M2) macrophages on pro-tumour phenotypes have been well documented in many cancers except hepatocellular carcinoma (HCC). Considering their close relationship with chronic tissue injuries as well as enhanced tumour invasiveness and growth, we aimed to investigate the direct effects of M2 macrophages on HCC., Methods: M2 macrophages in 95 HCC clinical specimens were quantified using immunohistochemistry and quantitative PCR. The pro-tumour functions and the underlying molecular mechanisms of M2 macrophages in HCC were investigated in vivo and in an in vitro co-culture system., Results: In the clinical study, high M2-specific CD163 (hazard ratio=2.693; p=0.043) and scavenger receptor A (hazard ratio=3.563; p=0.044) levels indicated poor prognosis and correlated with increased tumour nodules and venous infiltration in HCC patients. In an orthotopic model, the liver tumour volume was increased 3.26-fold (1.27 cm3±0.36) after M2 macrophage injection compared with the control (0.39 cm3±0.05) (p=0.032). An increased rate of lung metastasis was also found in the treatment group. In vitro, co-cultivation with M2 macrophages elevated the number of HCC cells (MHCC97L) and migration events by 1.3-fold and 3.2-fold, respectively (p<0.05). Strongly induced by MHCC97L, M2 macrophage-derived CCL22 was proven to enhance tumour migration capacities and correlate with venous infiltration in HCC patients. Increased epithelial-mesenchymal transition (EMT) via Snail activation in MHCC97L was found to be promoted by M2 macrophages and CCL22., Conclusions: M2 macrophages contribute to poor prognosis in HCC and promote tumour invasiveness through CCL22-induced EMT., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Published
- 2015
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47. Genome-wide identification of RNA editing in hepatocellular carcinoma.
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Kang L, Liu X, Gong Z, Zheng H, Wang J, Li Y, Yang H, Hardwick J, Dai H, Poon RT, Lee NP, Mao M, Peng Z, and Chen R
- Subjects
- Computational Biology methods, Genome-Wide Association Study, Humans, Sequence Analysis, RNA, Carcinoma, Hepatocellular genetics, Genome, Liver Neoplasms genetics, RNA Editing, Transcriptome
- Abstract
We did whole-transcriptome sequencing and whole-genome sequencing on nine pairs of Hepatocellular carcinoma (HCC) tumors and matched adjacent tissues to identify RNA editing events. We identified mean 26,982 editing sites with mean 89.5% canonical A→G edits in each sample using an improved bioinformatics pipeline. The editing rate was significantly higher in tumors than adjacent normal tissues. Comparing the difference between tumor and normal tissues of each patient, we found 7 non-synonymous tissue specific editing events including 4 tumor-specific edits and 3 normal-specific edits in the coding region, as well as 292 edits varying in editing degree. The significant expression changes of 150 genes associated with RNA editing were found in tumors, with 3 of the 4 most significant genes being cancer related. Our results show that editing might be related to higher gene expression. These findings indicate that RNA editing modification may play an important role in the development of HCC., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
48. Osteopontin Overexpression Induced Tumor Progression and Chemoresistance to Oxaliplatin through Induction of Stem-Like Properties in Human Colorectal Cancer.
- Author
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Ng L, Wan T, Chow A, Iyer D, Man J, Chen G, Yau TC, Lo O, Foo CC, Poon JT, Poon RT, Pang R, and Law WL
- Abstract
Colorectal cancer (CRC) is one of the most common and fatal malignancies worldwide. The poor prognosis of colorectal cancer patients is due to development of chemoresistance and cancer metastasis. Recently osteopontin (OPN) has been associated with stem-like properties in colorectal cancer. This study further examined the clinicopathological significance of OPN in CRC and its effect on chemoresistance and transcription of stem cell markers. We examined the transcription level of OPN in 84 CRC patients and correlated the expression with their clinicopathological parameters. The associations of OPN overexpression with transcription of stem cell markers and response to chemotherapy in DLD1-OPN overexpressing clones and CRC patients were also investigated. Our results showed that OPN was significantly overexpressed in CRC, and its overexpression correlated with tumor stage and poor prognosis. Overexpression of CRC induced OCT4 and SOX2 expression in vitro and correlated with SOX2 overexpression in CRC patients. In addition, DLD1-OPN overexpressing cells showed enhanced ability to survive upon oxaliplatin treatment, and OPN expression was higher in CRC patients who were resistant to oxaliplatin-involved chemotherapy treatment. Thus, CRC cells overexpressing OPN demonstrated stem-like properties and OPN inhibition is a potential therapeutic approach to combat CRC progression and chemoresistance.
- Published
- 2015
- Full Text
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49. Hepatocellular carcinoma: surveillance CT schedule after hepatectomy based on risk stratification.
- Author
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Liu D, Fong DY, Chan AC, Poon RT, and Khong PL
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular pathology, Contrast Media, Female, Humans, Liver Neoplasms pathology, Male, Middle Aged, Population Surveillance, Postoperative Complications pathology, Radiation Dosage, Retrospective Studies, Risk Factors, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular surgery, Hepatectomy, Liver Neoplasms diagnostic imaging, Liver Neoplasms surgery, Postoperative Complications diagnostic imaging, Tomography, X-Ray Computed methods
- Abstract
Purpose: To evaluate alternative schedules for surveillance computed tomography (CT) for patients who underwent hepatectomy for hepatocellular carcinoma ( HCC hepatocellular carcinoma ) and to demonstrate an appropriate schedule on the basis of stratification for risk of recurrence., Materials and Methods: CT and pathologic reports for consecutive patients with HCC hepatocellular carcinoma who underwent hepatectomy at one institution were evaluated with institutional review board approval. Univariate and multivariate analyses were performed to identify risk factors for recurrence. Patients were categorized into risk groups on the basis of classification and regression tree analysis. Average recurrence detection rates ( RDR recurrence detection rate s) between consecutive CT scans were calculated for existing and alternative surveillance schedules for each risk group, and the difference in RDR recurrence detection rate was determined by using the Student t test. A P value of less than .05 was considered to indicate a significant difference. Expected delay in diagnosis was also computed for the alternative surveillance schedules for each risk group., Results: Two hundred sixty patients (216 men; mean age, 56.0 years ± 22.5) underwent 2705 CT studies. Independent risk factors for recurrence were microvascular invasion (P = .001), cirrhosis (P = .007), and tumor multiplicity (P = .001). Three risk groups (low, intermediate, and high) were identified. For low- and intermediate-risk groups, average RDR recurrence detection rate was not significantly different in the first 2 years after hepatectomy when the interval was extended from 3 months (3.3% and 4.6%, respectively) to 4 months (4.3% [expected delay, 16 days] and 6.1% [expected delay, 18 days], respectively) or for the subsequent 3 years when the interval was extended from 6 months (1.3% and 3.5%, respectively) to 12 months (2.5% [expected delay, 72 days] and 7.0% [expected delay, 103 days], respectively). This alternative schedule included five (35.7%) fewer CT scans than the 14 in the original schedule, and a reduction in radiation dose and cost during the 5-year follow-up period., Conclusion: Posthepatectomy surveillance CT schedules may be tailored and optimized according to stratification by risk of recurrence to reduce the frequency of CT scans without compromising surveillance benefits.
- Published
- 2015
- Full Text
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50. Pancreaticoduodenectomy with vascular reconstruction for adenocarcinoma of the pancreas with borderline resectability.
- Author
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Cheung TT, Poon RT, Chok KS, Chan AC, Tsang SH, Dai WC, Chan SC, Fan ST, and Lo CM
- Subjects
- Adenocarcinoma mortality, Adenocarcinoma pathology, Adult, Aged, Aged, 80 and over, Female, Hospital Mortality, Humans, Kaplan-Meier Estimate, Male, Mesenteric Artery, Superior pathology, Mesenteric Artery, Superior surgery, Mesenteric Veins pathology, Mesenteric Veins surgery, Middle Aged, Neoplasm Invasiveness, Pancreatic Fistula etiology, Pancreatic Neoplasms mortality, Pancreatic Neoplasms pathology, Portal Vein pathology, Portal Vein surgery, Risk Factors, Time Factors, Treatment Outcome, Adenocarcinoma surgery, Pancreatic Neoplasms surgery, Pancreaticoduodenectomy adverse effects, Pancreaticoduodenectomy mortality, Plastic Surgery Procedures adverse effects, Plastic Surgery Procedures mortality, Vascular Surgical Procedures adverse effects, Vascular Surgical Procedures mortality
- Abstract
Aim: To analyze whether pancreaticoduodenectomy with simultaneous resection of tumor-involved vessels is a safe approach with acceptable patient survival., Methods: Between January 2001 and March 2012, 136 patients received pancreaticoduodenectomy for adenocarcinoma at our hospital. Seventy-eight patients diagnosed with pancreatic head carcinoma were included in this study. Among them, 46 patients received standard pancreaticoduodenectomy (group 1) and 32 patients received pancreaticoduodenectomy with simultaneous resection of the portal vein or the superior mesenteric vein or artery (group 2) followed by reconstruction. The immediate surgical outcomes and survivals were compared between the groups. Fifty-five patients with unresectable adenocarcinoma of the pancreas without liver metastasis who received only bypass operations (group 3) were selected for additional survival comparison., Results: The median ages of patients were 67 years (range: 37-82 years) in group 1, and 63 years (range: 35-86 years) in group 2. All group 2 patients had resection of the portal vein or the superior mesenteric vein and three patients had resection of the superior mesenteric artery. The pancreatic fistula formation rate was 21.7% (10/46) in group 1 and 15.6% (5/32) in group 2 (P = 0.662). Two hospital deaths (4.3%) occurred in group 1 and one hospital death (3.1%) occurred in group 2 (P = 0.641). The one-year, three-year and five-year overall survival rates in group 1 were 71.1%, 23.6% and 13.5%, respectively. The corresponding rates in group 2 were 70.6%, 33.3% and 22.2% (P = 0.815). The one-year survival rate in group 3 was 13.8%. Pancreaticoduodenectomy with simultaneous vascular resection was safe for pancreatic head adenocarcinoma., Conclusion: The short-term and survival outcomes with simultaneous resection were not compromised when compared with that of standard pancreaticoduodenectomy.
- Published
- 2014
- Full Text
- View/download PDF
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